XOMA Initiates Phase 2a Clinical Trial With XOMA 052 in Patients With Rheumatoid Arthritis

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XOMA Initiates Phase 2a Clinical Trial With XOMA 052 in Patients With

Rheumatoid Arthritis

Second Indication for Drug in Development for Type 2 Diabetes

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XOMA today announced the initiation of a Phase 2a clinical study evaluating

its product candidate XOMA 052, a potent monoclonal antibody targeting

interleukin-1 beta (IL-1 beta) for the treatment of rheumatoid arthritis.

IL-1 beta is a pro-inflammatory cytokine involved in the pathophysiology and

development of rheumatoid arthritis, diabetes, gout and other inflammatory

diseases. With this study, XOMA expands the development of XOMA 052 beyond

its ongoing efforts in Type 2 diabetes, where it has shown anti-inflammatory

and anti-diabetic effects in both preclinical and human studies.

The U.S.-based Phase 2a clinical study is a randomized, placebo-controlled

study designed to enroll up to 18 patients with moderate to severe

rheumatoid arthritis and evaluate the safety, pharmacokinetics and

disease-specific outcomes of XOMA 052. Standard rheumatoid arthritis

clinical assessment scores will be calculated using the American College of

Rheumatology core criteria which assess inflammatory status, joint physical

exam, and general patient functional status.

Patients will be enrolled into one of three groups. Each group will include

one patient who receives " standard of care " treatment plus placebo and five

who receive " standard of care " treatment plus a single dose of XOMA 052 at

0.3 milligrams per kilogram of body weight. In one group, XOMA 052 will be

administered by subcutaneous injection. In the other two groups, XOMA 052

will be administered by intravenous infusion. Patients will be followed for

eight weeks.

Rheumatoid arthritis is a chronic, multi-system autoimmune disease where the

cells of the immune system attack the joints, causing inflammation and joint

destruction which can be debilitating and reduces life expectancy. An

estimated two to three million patients in the U.S. are affected with

rheumatoid arthritis.

Engle, Chairman and Chief Executive Officer of XOMA, stated, " We

continue to be excited by the potential of XOMA 052 to address a number of

chronic diseases with major unmet medical needs. Last September, XOMA

presented encouraging results supporting one of the most significant medical

advances in diabetes in decades -- a move from insulin therapy to

anti-inflammatory treatment. The interim results from our diabetes trials

have provided the impetus to move into other inflammatory diseases such as

rheumatoid arthritis. This initial study is intended to build on our

encouraging diabetes results and on the anticipated results from clinical

studies evaluating other IL-1 blockers being evaluated in rheumatoid

arthritis. "

XOMA 052 Diabetes Study Results

In 2008, XOMA announced positive interim results from two Phase 1 clinical

studies evaluating five of six planned dose levels of XOMA 052. In the

studies, a single dose of XOMA 052 demonstrated biological activity in

patients with Type 2 diabetes as measured by standard measures of diabetes

and inflammatory markers for up to three months. The median glycosylated

hemoglobin (HbA1c) levels were reduced in all 5 dose groups, and the median

reduction was as much as 0.6 percent compared to baseline as measured 28

days following treatment. XOMA 052 reduced median HbA1c in 4 of 5 drug dose

levels when compared to placebo.

A single dose of XOMA 052 reduced levels of ultrasensitive C-reactive

protein, a standard measure of systemic inflammation, as compared to placebo

in all five of the dose groups. The studies support XOMA 052's novel

anti-inflammatory approach to Type 2 diabetes treatment that may preserve

insulin-producing cells.

The safety and pharmacokinetic results showed that XOMA 052 was well

tolerated at all five dose levels and had a potential dosing profile of once

per month or longer in Type 2 diabetes patients.

Recently announced preclinical results indicate that animals treated with

XOMA 052 have increased insulin production and proliferation of

insulin-producing islet cells. They also show decreased islet cell death,

reduced peripheral insulin resistance and lower cholesterol levels. There

was an absence of weight gain and hypoglycemic events.

Regulatory Approval of IL-1 blockers

The FDA has approved two drugs that use the IL-1 therapeutic approach. In

2001, the first drug, anakinra, was approved by the FDA for the treatment of

rheumatoid arthritis. As a result, a significant amount of information is

available about the safety of the IL-1 therapeutic approach. In 2008, the

FDA approved the second IL-1 drug, rilonacept, for cryopyrin-associated

periodic syndromes (CAPS), providing additional regulatory support for the

development of IL-1 therapeutics.

The positive clinical effect of the IL-1 therapeutic class of drugs was

demonstrated recently in two different indications. In 2008, two companies

announced positive results in Phase 2 studies of two IL-1 antibodies, one in

rheumatoid arthritis and another in Muckle-Wells disease. The anti-IL-1

antibodies in each study were reported to be well tolerated and to reduce

symptoms in patients. Clinical studies are being conducted in diabetes,

rheumatoid arthritis, gout and other diseases. XOMA believes these results

strengthen the medical hypothesis for the development of XOMA 052.

About XOMA 052

XOMA 052 is a potent monoclonal antibody with the potential to improve the

treatment of patients with a wide variety of inflammatory diseases. XOMA 052

binds strongly to Interleukin-1 beta (IL-1 beta), a pro-inflammatory

cytokine that is involved in the development of diabetes, rheumatoid

arthritis, gout, and other diseases. By binding to IL-1 beta, the drug

inhibits the activation of the IL-1 receptor, thereby preventing the

cellular signaling events that produce inflammation. XOMA 052 is a humanized

IgG2 antibody with a half-life of 22 days. Based on its binding properties,

specificity to IL-1 beta and half-life, XOMA 052 may provide convenient

dosing of once per month or longer. XOMA 052 was developed by XOMA using the

Company's proprietary antibody technologies, capabilities and expertise.

XOMA owns worldwide rights to the antibody and related intellectual

property.

About Interleukin-1 and Inflammatory Disease

IL-1 is a pro-inflammatory cytokine secreted by a number of cell types

including monocytes and macrophages. The IL-1 gene family includes IL-1

beta, which is released from cells as part of an inflammatory reaction. IL-1

beta produces a range of biological effects, mainly through the induction of

other pro-inflammatory mediators such as corticotrophin, platelet factor-4,

prostaglandin E2 (PGE2), IL-6, and IL-8. IL-1 beta induces both local and

systemic inflammatory effects through the activation of the IL-1 Type 1

receptor found on almost all cell types. IL-1 beta is implicated in the

pathogenesis of many disease states involving localized and systemic

inflammation. Targeting this pathway and reducing the effects of IL-1 beta

may provide clinical benefit in rheumatoid arthritis, systemic juvenile

idiopathic arthritis, osteoarthritis, and other inflammatory diseases.

About XOMA

XOMA discovers, develops and manufactures therapeutic antibody and other

agents designed to treat inflammatory, autoimmune, infectious and cancerous

diseases. The company's proprietary product pipeline includes XOMA 052, an

anti-IL-1 beta antibody, and XOMA 3AB, a biodefense anti-botulism antibody

candidate.